Lung transplant rejection: post-treatment cell-free DNA levels predict allograft failure

Authors

• AY Lin
• MB Keller
• MK Jang
• H Kong
• W Park
• X Tian
• S Agbor-Enoh

Abstract

Lung transplant patients show the lowest survival among all solid organ transplants, primarily from chronic lung allograft dysfunction (CLAD). With no available therapies, CLAD prevention is the cornerstone to improve survival. Despite treatment of the major risk factors such as Acute rejection (AR) and organizing pneumonia (OP), CLAD still develops at high rates. It is unknown whether the degree of molecular allograft injury following treatment of AR/OP modulates risk of CLAD and death. In the multicenter Genomic Research Alliance for Transplantation (GRAfT) cohort study, we quantified the degree of molecular allograft injury by longitudinal measures of plasma donor-derived cell-free DNA (dd-cfDNA), a novel molecular biomarker of allograft injury, and assessed the association of mean dd-cfDNA levels after AR/OP with the risk of CLAD/death. Among 205 patients undergoing lung transplantation between 2015 and 2021, 93 patients had AR/OP and dd-cfDNA levels measured within 3 to 6 months following the diagnosis. In multivariable proportional hazards regression analysis adjusting for patient/transplant risk factors, mean dd-cfDNA levels after AR/OP were independently associated with an increased risk of CLAD and death (HR 3.53, 95% CI 1.76 – 7.98, p < 0.001 for CLAD/death; HR 3.07, 95% CI 1.40 – 6.77, p = 0.005 for CLAD; HR 4.48, 95% CI 1.79 – 11.2, p = 0.001 for death). The association of dd-cfDNA following AR/OP with CLAD and death underscore the potential utility of dd-cfDNA as a tool for improving risk stratification, monitoring the resolution of allograft injury and assessment of treatment responses for lung transplant patients.

Scientific Focus Area: Clinical Research

This page was last updated on Tuesday, August 6, 2024